Map30 is an anti-HIV and anti-tumor protein extracted from the mature fruits and seeds of Momordica charantia (bitter melon). The protein is a member of the family of ribosomal inactivating proteins (RIP) of which the ricin A chain, RCA, is the best known. All RIP family members have a highly specific RNA N-glycosylase (RNG) activity against 28S rRNA. However, many RIPs have been reported to depurinate and cleave DNA, while MAP30 has been reported to inhibit HIV integrase, an activity not shared by other RIPs. In order to understand MAP30 functionality at the molecular level, we have determined its three dimensional solution structure from a total of 3500 distance, dihedral angle and dipolar coupling restraints; at 30kDa MAP30 is one of the largest proteins whose solution structure has been determined without a prior X-ray structure. The fold of MAP 30 is quite similar to the structures other RIPs whose crystal structures are available. A comparison of RIP structures shows that the sidechain of a strictly conserved Trp residue (W190 in MAP30) is on the protein surface, adjacent to the RNG active site. We have shown that HIV LTR DNA binds at this site, and propose that DNA is depurinated at this active site. Apurinic DNA is expected to have greatly enhanced binding affinity towards Trp190, based upon studies of peptide binding to depurinated DNA. Binding to Trp190, brings the apurinic DNA site close to a lysine sidechain in Map30, in PAP and in gelonin, three RIPs reported to have deglycosylase/apurinic lyase (DGAL) activity. This enables the lysine sidechain amino group to function as an attacking nucleophile, similar to amino groups identified in DNA DGAL enzymes and in peptides that cleave DNA at apurinic sites. Neither of the two Lys amino groups in the RCA is close to the conserved Trp. While the RCA has been reported to depurinate DNA, it shows no evidence of ap lyase activity. We therefore suggest that RIPs utilize a common active site to depurinate both DNA and 28SrRNA. Furthermore, we propose that, after depurination, the apurinic DNA site binds to W190, facilitating attack on the DNA apurinic site by a nearby Lys sidechain. Hence, in our model, DNA depurination and cleavage reactions take place at distinct, but contiguous, sites on the RIP surface. Note, apurinic DNA cleavage activity involving other surface aromatic sidechains, close to lysine amino groups, is possible. Finally we suggest that the reported inhibition of HIV integrase by MAP30 is due to competition of MAP30 and the integrase for a common DNA substrate.